RESUMO
BACKGROUND: Hypercalcemia is the most common of all paraneoplastic syndromes and has been reported to appear in up to 20% of patients with renal cell carcinoma (RCC). Humoral hypercalcemia of malignancy is believed to be induced when parathyroid hormone-related protein (PTHrP) is excessively produced in cancer cells and impairs the homeostasis of serum calcium concentrations. METHODS: Cancer cells were isolated from a surgical specimen and successfully cultured in a monolayer. The present study describes the establishment and characterization of new cell lines of RCC. RESULTS: Two different cell lines, designated SMRC-1 and SMRC-3, were established from human RCC, each of which had been continuously secreting PTHrP in vitro. The patient from whom the SMRC-3 cells were obtained was shown to have elevated levels of PTHrP and resultant hypercalcemia. Cultured SMRC-1 was spindle-shaped in morphology. SMRC-3 had pleomorphic polygonal shapes and formed typical epithelial monolayers. Both cell types secreted intact, C-terminal PTHrP and interleukin-6 in the culture medium. Cellular messenger RNA of PTHrP was analyzed by reverse transcriptase-polymerase chain reaction. The SMRC-1 cells showed chromosome numbers ranging from 42 to 47 with consistent structural abnormalities of add(4)(q23~25) and add(6)(q13). The chromosomal analysis of SMRC-3 revealed a modal number of 95 with consistent structural abnormalities of add(1)(p36) and der(1;3)(q10;p10). CONCLUSIONS: These cell lines could be good models for investigating the mechanism of PTHrP production and the relationship between this hormone and hypercalcemia.
Assuntos
Carcinoma de Células Renais/metabolismo , Neoplasias Renais/metabolismo , Biossíntese de Proteínas , Células Tumorais Cultivadas/metabolismo , Adulto , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Divisão Celular , Aberrações Cromossômicas , Cromossomos Humanos Par 1 , Humanos , Hipercalcemia/metabolismo , Interleucina-6/metabolismo , Cariotipagem , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Proteína Relacionada ao Hormônio Paratireóideo , Proteínas/genética , Proteínas/metabolismo , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas/citologiaRESUMO
BACKGROUND: ACT-1, a new cell line of human adrenocortical carcinoma, has been established and successfully maintained in culture. This study examined the biological characteristics of the cells. METHODS: The tumor cells were isolated from a surgical specimen of the tumor thrombus and cultured in monolayer. RESULTS: Histologically, the primary tumor was composed of a solid proliferation of large polygonal cells. A part of the atrophic adrenal cortex remained at the periphery of the tumor. The cultured ACT-1 cells were spindle-shaped in morphology and grew exponentially with an approximate population doubling time of 24 h. A chromosomal analysis revealed a modal number of 61 with consistent structural abnormalities of add(3)(q11), add(9)(p11), and add(16)(ql1). The expression of 3beta-hydroxysteroid dehydrogenase was observed in the ACT-1 cells as well as in normal human adrenal glands. CONCLUSIONS: The ACT-1 cell line provides a reproducible model system which gives good insight into the oncogenesis of adrenocortical carcinoma.
